Long-Term Treatment with Empagliflozin Attenuates Renal Damage in Obese Zucker Rat

Abstract

Introduction Empagliflozin, a known inhibitor of sodium-glucose cotransporter type 2 (SGLT2) decreases glucose reabsorption by the renal tubules and promotes glucose excretion into the urine. While the effectiveness of Empagliflozin in the management of hyperglycemia along with associated cardiovascular and all-cause mortality has been demonstrated previously, the therapeutic benefits associated with the long-term use of this drug in obese animals have yet to be investigated. Methods Male 5-week-old lean and obese Zucker rats were randomly assigned to one of the 4 groups- lean control, lean treated, obese control, obese treated and treated with either Empagliflozin (10 mg/kg BW / day) or placebo for 25 weeks to investigate the therapeutic effect of Empagliflozin. Results Empagliflozin treatment in the obese animals was associated with decreased body weight, attenuated the loss of F-actin from the renal tubules and improved renal structure and function. These changes in renal function were associated with significant improvements in the glucose tolerance, and decreased non-fasting circulatory levels of glucose, amylase, and other inflammatory markers including NGAL, cystatin C, and clusterin. Conclusion Long-term use of Empagliflozin in diabetic obese Zucker rats is associated with improvements in glucose tolerance and decreased loss of renal structure and function.

Empagliflozin Contributes to Polyuria via Regulation of Sodium Transporters and Water Channels in Diabetic Rat Kidneys

“…In addition, it may not be easy to affirm that changes of sodium and water transporters/channels shown in this study are from direct or indirect effects of empagliflozin. Interestingly, the insulin-dependent action and extra-metabolic benefits of SGLT2 inhibitors, including reduction of albuminuria, fibrosis, oxidative stress and inflammation in diabetic or obese rat kidneys, have been recently suggested although the mechanism underlying other renal effects beyond their SGLT2 inhibition remains unexplained (Lee et al, 2018; Manne et al, 2019). Thus, the possibility that the pleiotropic effect of SGLT2 inhibitors affects renal tubules and interstitium cannot be excluded.…”

Sodium-glucose cotransporter 2 inhibition prevents renal fibrosis in cyclosporine nephropathy

“…In fact, in non-diabetic preclinical models of nephropathies, dapagliflozin, a SGLT2 inhibitor, reduced proteinuria and podocyte damage [ 22 ], and empagliflozin, a SGLT2 inhibitor, improved renal function in obese Zucker rats [ 23 ], reduced renal dysfunction and fibrosis in unilateral ureteric obstruction [ 24 ], regulated the circadian rhythm of blood pressure in salt-treated obese rats [ 25 ], and finally prevented the development of renal fibrosis through an anti-inflammatory mechanism in Ang II-dependent hypertension [ 26 ]. Conversely, empagliflozin did not show nephroprotection in a murine model of oxalate-related nephrocalcinosis [ 27 ] and dapagliflozin did not modify proteinuria and renal fibrosis in 5/6 subtotally nephrectomized rats [ 28 ].…”

Gut micobiota alteration by Lactobacillus rhamnosus reduces pro-inflammatory cytokines and glucose level in the adult model of Zebrafish

“…Metabolic syndrome has steadily increased globally and many etiological factors including altered inflammatory states, adipose abnormalities and insulin resistance, contribute to their pathogenesis and thus should be considered in related basic studies [ 1 – 3 ]. Diabetes mellitus (DM) which is known by glycemic disturbances is usually categorized to various categories.…”